Co-registered photoacoustic and ultrasound imaging for non-invasive ovarian cancer diagnosis and risk management Abstract Worldwide, the estimated annual incidence of ovarian cancer is 204,000, with 125,000 deaths. Despite advances in therapy, ovarian cancer remains the most deadly of the gynecological cancers. Less than 30% of women with advanced stage disease survive long-term. One of the reasons for the high fatality rate is that more than 70% of women with ovarian cancer are diagnosed with advanced disease. Photoacoustic tomography is an emerging technology that maps tumor vasculature content and oxygen saturation, which are functional biomarkers of malignant development. Using co-registered photoacoustic tomography (PAT) and ultrasound (US), we have developed a new noninvasive transvaginal imaging device for non-invasive diagnosis of ovarian cancer. Initial data have shown that co-registered PAT/US identifies invasive epithelial ovarian cancers by demonstrating extensively distributed and higher levels of relative total hemoglobin (rHbT) in the US-identified region of interest (ROI), as compared with more scattered and lower levels of relative total hemoglobin in benign and normal ovaries (p=0.01). PAT/US identifies invasive epithelial ovarian cancers, as well as non-invasive borderline and stromal tumors, by differentiating the lower SO2 in the US-identified ROI from the higher values in benign and normal ovaries (p=0.003). In this proposed work, we will 1) optimize our co-registered photoacoustic and ultrasound system and user interface, 2) develop and validate classification models using photoacoustic functional imaging biomarkers, PAT/US spectral features, and the known biomarker CA125, and 3) develop light fluence correction algorithms for quantitative photoacoustic imaging to characterize ovarian tissue vasculature. We will prospectively assess the ability of co-registered PAT/US to assist conventional imaging for more accurate diagnosis of ovarian cancers and reduction of benign surgeries, without compromising cancer detection. We will also monitor a group of high-risk women to determine if co-registered PAT/US can be used as a potential sensitive and specific screening tool to differentiate normal from early angiogenesis changes of the malignant process. The successful completion of the project will provide a means to improve the current clinical practice.